Photochromic channel blockers provide a conceptually simple and convenient way to modulate neuronal activity with light. We have recently described a family of azobenzenes that function as tonic blockers of K(v) channels but require UV-A light to unblock and need to be actively switched by toggling between two different wavelengths. We now introduce red-shifted compounds that fully operate in the visible region of the spectrum and quickly turn themselves off in the dark. Furthermore, we have developed a version that does not block effectively in the dark-adapted state, can be switched to a blocking state with blue light, and reverts to the inactive state automatically. Photochromic blockers of this type could be useful for the photopharmacological control of neuronal activity under mild conditions.

L-type Ca channels (LTCCs) play a crucial role in excitation-contraction coupling and release of hormones from secretory cells. They are targets of antihypertensive and antiarrhythmic drugs such as diltiazem. Here, we present a photoswitchable diltiazem, FHU-779, which can be used to reversibly block endogenous LTCCs by light. FHU-779 is as potent as diltiazem and can be used to place pancreatic β-cell function and cardiac activity under optical control.

Nitidasin is a pentacyclic sesterterpenoid with a rare 5-8-6-5 carbon skeleton that was isolated from the Peruvian folk medicine "Hercampuri". It belongs to a small class of sesterterpenoids that feature an isopropyl trans-hydrindane moiety fused to a variety of other ring systems. As a first installment of our general approach toward these natural products, we report the total synthesis of the title compound. Our stereoselective, convergent route involves the addition of a complex alkenyl lithium compound to a trans-hydrindanone, followed by chemoselective epoxidation, ring-closing olefin metathesis, and redox adjustment.

Light control of voltage‐gated ion channels: We have developed red‐shifted derivatives of QAQ, a powerful doubly charged photochromic blocker. These derivatives allow for remote control of Kv and Nav channel conductance with light and offer the opportunity to silence neuronal activity reversibly.

Astellatol and nitidasin belong to a subset of sesterterpenoids that share a sterically encumbered trans-hydrindane motif with an isopropyl substituent. In addition, these natural products feature intriguing polycyclic ring systems posing significant challenges for chemical synthesis. Herein, we detail the evolution of our stereoselective strategy for isopropyl trans-hydrindane sesterterpenoids. Our endeavors included the synthesis of several building blocks, enabling studies toward all molecules of this terpenoid subclass, and of advanced intermediates of our initial route toward a biomimetic synthesis of astellatol. These findings provided the basis for a second-generation and a third-generation approach toward astellatol that eventually culminated in the enantioselective total synthesis of (−)-nitidasin. In particular, we orchestrated a series of substrate-controlled transformations to install the ten stereogenic centers of the target molecule and forged the carbocyclic backbone in a convergent fashion. Furthermore, we disclose our progress toward the synthesis of astellatol and provide insights into some observed yet unexpected diastereoselectivities by detailed quantum-mechanical calculations.

Nitidasin, ein komplexes Sesterterpenoid mit einem seltenen 5-8-6-5-Kohlenstoffgerüst, wurde aus dem peruanischen Naturheilmittel "Hercampuri" isoliert und ist ein Vertreter einer kleinen Gruppe von polycyclischen Sesterterpenoiden, die eine trans-Hydrindaneinheit mit einem Isopropylsubstituenten aufweisen. Als erstes Ergebnis unseres allgemeinen Ansatzes zur Synthese solcher Naturstoffe stellen wir die Totalsynthese der Titelverbindung vor. Die Schlüssel-sequenz unserer stereoselektiven und konvergenten Route besteht aus der Addition einer komplexen Alkenyllithiumverbindung an ein trans-Hydrindanon, einer chemoselektiven Epoxidierung und einer Ringschlussmetathese.

Seveml recent advances in microwave coaxial connectors offer possibilities of m j o r i n p r o v e m t s i n coaxial measuremnt accuracy and circuit per€omm e . I n this session three papers on new precision connectors and related components are presented followed by a panel discussion of these devices and t h e i r probable impact on msurements, compnent developmnt, and system design. Also, the panel w i l l present views on the order-of-magnitude improverrrents nm possible in Type N, TNC, a d other c o m n connectors. The panel mmkrs are well-hm, qualified experts currently involved in advancing coaxial techniques. R. C. P m e l l , National wII.eau of Standards , Boulder , Cola. R. A. W m , Gene& Radio company, Bolton, kss. B. 0. Weinschel , Weinschel Engineering, Gaithersburg, €43.

In the version of this Brief Communication originally published, the commercial human cardiomyocytes used in the study (Cor4U, NCardia AG) were believed to be derived from human induced pluripotent stem cells during the studies. After studies had been completed, short tandem repeat testing by NCardia determined that Cor4U cardiomyocytes were derived from the human embryonic stem cell line RUES2, which have been shown to produce functional cardiomyocytes (Chong, J. J. H. et al. Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts, Nature 510, 273-277 (2014)). The correction has been reflected in a change in the first sentence of the Methods section 'Recording of field potentials (FPs) with a multi-electrode array (MEA) from cardiomyocytes with localized FHU-779 switching' . The different provenience of these well characterized cardiomyocytes likely does not change the findings nor the interpretation of the data.